Born to Andalusian parents, who moved to North Africa to escape the fascism of Francisco "El Caudillo" Franco, he moved to France at age 17. His career started in French movies, where he appeared in many of Luc Besson's films, two of which brought huge success for him as well: The Big Blue (1988), Leon (1994), known as the Professional in the US. He played in the American movies French Kiss (1995) with Meg Ryan and Kevin Kline, Mission: Impossible (1996) with Tom Cruise, Ronin (1998) with Robert De Niro, while not neglecting French productions either—e.g., The Visitors (1996) and The Crimson Rivers (2000).

He was married twice and has four children, two from each marriage. His first wife was Genevieve, with whom he had a daughter, Sandra (born in 1978), and a son, Mickael (born in 1980). His second wife was Nathalie Dyszkiewicz, with whom he had a son, Tom (born 1996), and a daughter, Serena (born 1998). He maintains homes in Paris and in Los Angeles.

Reno was also involved in the production of the second sequel of the popular PlayStation 2 series Onimusha (Onimusha 3: Demon Siege), having his likeness created into the protagonist Jacques Blanc as well as providing the voice for the character.